This invention relates to a process for the preparation of substituted or unsubstituted arylalkylamines from substituted or unsubstituted arylalkyl ketones by nitrosation to form an aryl o-oximinoalkylketone followed by hydrogenation reduction of the oximino group to an amine and dehydroxylation of an hydroxyl group produced by hydrogenation reduction of the keto group.
Substituted and unsubstituted arylalkylamines are chemical intermediates of great importance. They are used in the preparation of pharmacologically active compounds and in some instances are themselves pharmacologically active. For example, phenethylamine and p-hydroxyphenethylamine (tyramine) have sympathomimetic (adrenergic) action. Tyramine also is a moiety in opiates, and is useful as an intermediate or substituent in the preparation of other physiologically active compounds or compositions. Hydroxyltyramine (dopamine) is a physiologically important neural inhibitory transmitter.
In U.S. Pat. Nos. 1,995,709 and 2,567,906 by Hartung, a multi-operations procedure for the preparation of substituted phenylpropanol amines is described, particularly, for 1-(p- or m-hydroxyphenyl)-2-amino-1-propanol (in U.S. Pat. No. 1,995,709), and 1-(p-aminophenyl)2-amino-1-propanol (in U.S. Pat. No. 2,507,906). In U.S. Pat. No. 1,995,709, p- or m-hydroxypropiophenone is reacted with a lower alkyl nitrite in ether in the presence of hydrogen chloride to produce p- or m-hydroxyisonitrosopropiophenone, which then is separated from the reaction mixture by alkaline extraction and recovered from the alkaline solution by precipitation induced by acidification of the extract, after which the precipitate is recrystallized. The p- or m-hydroxyisonitrosopropiophenone thus separated is then reacted with hydrogen in the presence of palladium on charcoal in absolute alcohol containing dry hydrogen chloride until reduction stops, after which the amino ketone is recovered as a filtrate. The filtrate is dryed and purified by recrystallization. Then the amino ketone is dissolved in water and reacted with hydrogen in the presence of palladium on charcoal. The reaction product is recovered as the hydrochloride of the amino alcohol, for example, the hydrochloride of 1-(p-hydroxyphenyl)-2-aminopropanol (in U.S. Pat. No. 1,995,709) and the hydrochloride of 1-(p-aminophenyl)-2-aminopropanol (in U.S. Pat. No. 2,507,906).
In U.S. Pat. No. 2,505,645 by McPhee, the acidic catalytic hydrogenation process described by Hartung is employed in a method of preparing .alpha.-phenyl-.beta.-hydroxyphenyl.beta.-hydroxyethylamine.
U.S. Pat. No. 2,784,228 by Hartung describes an also partially aqueous alternative process for the catalytic reduction of .alpha.-oximino ketones, using alkaline solutions instead of acidic solutions to obtain a desired amino alcohol. Difficulties and shortcomings of the acidic catalytic reduction process described by Hartung in U.S. Pat. Nos. 1,995,709 and 2,567,906 are detailed by Hartung in U.S. Pat. No. 2,784,228 and also by Wilbert et al. in U.S. Pat. No. 3,028,429. In U.S. Pat. No. 3,028,429, Wilbert et al. describe a process for the hydrogenation of isonitrosopropiophenone to produce 1-phenyl-2-aminopropanol which is a modification said to improve yields respecting the general process described by Hartung in U.S. Pat. Nos. 1,995,709 and 2,567,906.
In U.S. Pat. No. 3,966,813 by Satzinger et al. hydroxyacetophenone is reacted with a lower alkyl nitrite in a dipolar aprotic solvent in the presence of a hydrogen chloride catalyst to form m- or p-hydroxyisonitrosoacetophenone. The reaction mixture containing the isonitroso compound is poured into ice water and extracted with ethyl acetate. The ethyl acetate solution is dried, cleaned with charcoal, filtered, and vacuum distilled to recover the compound. After recrystallization, the compound is then catalytically hydrogenated to reduce the isonitroso and keto moieties of the hydroxyisonitrosoacetophenone to form 1-(m- or p-hydroxyphenyl)-2-amino-1-ethanol. The catalytic hydrogenation disclosed is conducted in an aqueous ethanol solution in the presence of hydrochloric acid in aqueous solution using a palladium on charcoal catalyst.
In a procedure described by Cannon, J. G. et al. in J. Med. Chem., V.25, p. 1442 (1982), 4, 5-dimethoxy-1-indanone is reacted with n-butylnitrite in methanol and upon acidification with HCl, 4,5-dimethoxy-2-oximino-1-indanone is recovered as a precipitate. This is added to a major amount of glacial acetic acid and a minor amount of concentrated sulfuric acid and hydrogenated over a palladium on carbon catalyst to produce 4,5-dimethoxy-2-aminoindan hydrochloride, which is then recovered.
Tyramine is described in the literature as produced by the sodium in ethanol reduction of p-hydroxyphenylmethyl cyanate, J. Chem. Soc. v.95, p.1127 (1909); by the platinum catalyzed hydrogenation of p-hydroxyphenylmethylcyanate, Buck J. S., J. Am. Chem Soc. v.55, p.3389 (1933); and by a lactobacillus decarboxylation of 1-(p-hydroxyphenyl)-2-aminopropionic acid, Umezi, M. et al., Hakko Kooaku Kaishi. v.55(2), p.68-74 (1977).
The following U.S. Patents involve various aspects of hydroxyphenethylamine or tyramine but do not disclose the process of this invention: U.S. Pat. Nos. 4,885,312; 4,868,218; 4,868,132; 4,861,800; 4,857,522; 4,762,781; 4,699,782; 4,686,179; 4,623,485; 4,609,544; 4,563,263; 4,515,773; 4,503,147; 4,496,655; 4,465,775; 4,436,828; 4,370,495; 4,277,460; 4,207,308; 4,190,593; 4,175,136; 4,032,406; 3,997,608; 3,997,525; 3,993,436; 3,981,982; 3,932,461; 3,894,051; 3,818,015; 3,676,447; 3,576,808; 3,457,354; and 2,695,297.